Whitlock Reid, MacDonald Kerry, Tangri Navdeep, Walsh Michael, Collister David
Chronic Disease Innovation Centre, Winnipeg, MB, Canada.
University of Manitoba Libraries, Winnipeg, MB, Canada.
Can J Kidney Health Dis. 2024 Oct 8;11:20543581241283523. doi: 10.1177/20543581241283523. eCollection 2024.
The efficacy and safety of bisphosphonate therapy for the treatment of osteoporosis and osteopenia in the setting of chronic kidney disease (CKD) is unclear.
To determine the effect of bisphosphonate therapy on fractures, bone mineral density (BMD), and adverse events in adults across the spectrum of CKD and dialysis.
Systematic review and individual patient-level meta-analysis.
Searches of Ageline, CINAHL, the Cochrane Library, EMBASE, and Medline from inception to August 25, 2016, supplemented with manual screening and clinicalstudydatarequest.com. Authors were contacted for individual patient-level data.
Randomized, placebo-controlled trials with 100 or more participants that evaluated the treatment of primary osteoporosis/osteopenia in adult men and women with bisphosphonate therapy.
Study characteristics, quality, and data were assessed independently by 2 reviewers. Outcome measures were fractures, BMD, and adverse events including decline in estimated glomerular filtration rate (eGFR) and hypocalcemia (calcium <2.00 mmol/L).
Single-stage individual patient-level meta-analysis.
Of 39 eligible studies, individual patient-level data was available for 7 studies, all of which were studies of ibandronate. Of 7428 participants (5010 ibandronate, 2418 placebo), 100% were female, 98.6% were white, the mean body mass index was 25.7 kg/m (SD 3.9), 18.9% were smokers and there were 740 fracture events. The mean eGFR was 69.1 mL/min/1.73 m (SD 15.9) including 14.5%, 54.9%, 27.5%, 3.0%, and 0.2% stages G1, G2, G3A, G3B, and G4 CKD. Ibandronate increased hip and lumbar spine BMD and decreased the risk of fracture in the overall population (hazard ratio (HR) 0.871, 95% confidence interval (CI) 0.746, 1.018) but in patients with stage G3B CKD, it increased the risk of fracture (HR 3.862, 95% CI 1.156, 12.903). Ibandronate did not impact eGFR over 12 months but increased the risk of hypocalcemia (HR 1.324, 95% CI 1.056, 1.660) with no evidence of any effect modification by CKD stage (all tests of interaction > 0.05).
Clinically significant heterogeneity among studies, lack of long-term follow-up and bone biopsy results, limited representation of stage G4 and G5 CKD patients.
Chronic kidney disease potentially modifies the efficacy but not the safety of bisphosphonate therapy in osteopenia and osteoporosis.
PROSPERO CRD42020145613.
双膦酸盐疗法用于治疗慢性肾脏病（CKD）患者的骨质疏松症和骨质减少症的疗效及安全性尚不清楚。
确定双膦酸盐疗法对整个CKD及透析范围内成年患者骨折、骨矿物质密度（BMD）和不良事件的影响。
系统评价和个体患者水平的荟萃分析。
检索了自数据库建立至2016年8月25日的Ageline、CINAHL、Cochrane图书馆、EMBASE和Medline，并辅以人工筛选和clinicalstudydatarequest.com。与作者联系获取个体患者水平的数据。
纳入100名或更多参与者的随机、安慰剂对照试验，这些试验评估了双膦酸盐疗法对成年男性和女性原发性骨质疏松症/骨质减少症的治疗效果。
由2名审阅者独立评估研究特征、质量和数据。结局指标为骨折、BMD和不良事件，包括估计肾小球滤过率（eGFR）下降和低钙血症（血钙<2.00 mmol/L）。
单阶段个体患者水平的荟萃分析。
在39项符合条件的研究中，7项研究有个体患者水平的数据，所有这些研究均为关于伊班膦酸钠的研究。在7428名参与者中（5010名接受伊班膦酸钠治疗，2418名接受安慰剂治疗），100%为女性，98.6%为白人，平均体重指数为25.7 kg/m²（标准差3.9），18.9%为吸烟者，共有740例骨折事件。平均eGFR为69.1 mL/min/1.73 m²（标准差15.9），其中G1、G2、G3A、G3B和G4期CKD患者分别占14.5%、54.9%、27.5%、3.0%和0.2%。伊班膦酸钠增加了总体人群的髋部和腰椎BMD，并降低了骨折风险（风险比（HR）为0.871，95%置信区间（CI）为0.746，1.018），但在G3B期CKD患者中，它增加了骨折风险（HR为3.862，95%CI为1.156，12.903）。伊班膦酸钠在12个月内未影响eGFR，但增加了低钙血症风险（HR为1.324，95%CI为1.056，1.660），且没有证据表明CKD分期对其有任何效应修饰作用（所有交互作用检验P>0.05）。
研究间存在临床显著异质性，缺乏长期随访和骨活检结果，G4和G5期CKD患者的代表性有限
